Several aspects of the present invention relate, in general, to a potentiostat and a biosensor circuit employing the potentiostat. The invention provides a multi-channel biosensor circuit having a potentiostat that enables sequential and simultaneous measurements to be performed at different cells across an array of biosensing devices.
1. Field of the Invention
A potentiostat is a measurement apparatus commonly used in the electrochemical field for executing voltammetric techniques. Cyclic voltammetry is a particularly useful voltammetric technique and aids the study of reversible reduction-oxidation (redox) reactions. When such techniques are applied to the biosensing field, a reversible redox reaction can take place at the interface between the surface of a biosensor selective receptive membrane (a bioreceptor) and an electrolyte.
2. Description of the Related Art
Three examples of known potentiostat circuits are illustrated in FIGS. 1a to 1c. FIG. 2 is a cross-sectional schematic diagram of a sample undergoing cyclic voltammetric measurement using a potentiostat circuit of FIG. 1. Referring to FIG. 1, a potentiostat circuit 1000 is connected to a counter electrode CE, a reference electrode RE and a working electrode WE. As best shown in FIG. 2, the circuit is completed by a buffer solution containing samples under test, hereunder referred to as an analyte or electrolyte 1001, which is represented by a resistor 1020 in FIGS. 1a to 1c and a bioreceptor layer 1015, which is represented as a capacitor and resistor 1025 connected in parallel in FIGS. 1a to 1c. The reference electrode is separated from the working electrode WE by an insulating layer 1030 of, for example, Si3N4 in FIG. 2. The reference electrode RE draws no current and is positioned in close proximity to the working electrode WE in order to measure the voltage at the surface of the bioreceptor layer 1015 and close the feedback loop for a first operational amplifier A1. Once the feedback loop is closed, the high gain at the first operational amplifier A1 ensures that the voltage at the reference electrode, and hence the voltage at the surface of the bioreceptor layer 1015, with respect to the voltage at the working electrode equals VSCAN, as shown in FIGS. 1a and 1b, or —(R2/R1) VSCAN, as shown in FIG. 1c. 
The bioreceptor layer 1015 may be a phage or enzyme that binds with a predetermined DNA or RNA strand, a peptide or another biological molecule, thereby changing the resistance and/or the capacitance of the circuit in which the electrodes are connected. Commonly the bioreceptor layer 1015 is known as a probe and the selective biological molecule it interacts with as a target. The characteristics of the capacitance and resistance as functions of applied voltage across them (in this case VSCAN) vary if the target biological molecule bonds or reacts with the phage or the enzyme provided as the bioreceptor layer 1015, allowing the presence of the biological molecule to be detected. Specifically, the potentiostat circuit measures the current at the working electrode WE while a time varying voltage (reflected as the voltage at the reference electrode RE) and equal to VSCAN in the examples as shown in FIGS. 1a and 1b is applied at the surface of the bioreceptor layer .
A time varying periodic voltage signal is typically used as VSCAN in FIGS. 1a to 1c. This is beneficial when the potentiostat circuit is being used to measure a redox reaction, since the use of a DC voltage may affect the reaction. As VSCAN oscillates, the first half cycle promotes a reduction/oxidation reaction at the interface and the second half cycle promotes an oxidation/reduction reaction at the interface. As VSCAN varies, the rate of the reduction/oxidation reaction varies. At some points the reduction and oxidation reaction rates are at their maximum due to a diffusion of charge carrying species occurring due to the concentration gradient. The required charge transfer is supplied/removed at the working electrode. In operation, the reduction and oxidation reaction cycles are observed as a time varying current flow, IOUT(t) measured at the working electrode WE versus a cycle of scanning voltage, VSCAN(t). The voltage at the working electrode can be held at any DC reference level. The output of the circuit is typically a hysteresis loop with peaks pointing in opposite directions, as shown in FIG. 3. The shape of the hysteresis loop indicates whether a particular redox reaction has taken place, whether it is reversible and enables a user to study the rate of reaction by adjusting the scan rate dependency. The locations and magnitudes of the peaks are results of the reactants in equilibrium during the charge transfer that occurs in a redox reaction, and hence can be employed to extract the concentration of species in the analyte.
A multi-channel potentiostat circuit is required for the analysis of a matrix of samples or to perform analysis a sample using a, matrix of bioreceptors. A known multi-channel potentiostat circuit is illustrated in FIG. 4. Referring to FIG. 4, a number of different matrix elements cell 1, cell 2, cell N, each share a common analyte or electrolyte. With such an arrangement, the counter electrodes CE of each matrix element cell 1, cell 2, . . . , cell N are connected together, meaning that effectively a single counter electrode CE is used. Each matrix element comprises a reference electrode RE disposed close to the surface of a bioreceptor layer (not shown in FIG. 4) and a working electrode WE with specific properties such as current sensitivity and dynamic range for the bioreceptor layer. Since each matrix element shares the same feedback loop between the counter electrode and each reference electrode, only one matrix element at a time may be used if the reference electrode is to be held at a required cyclic voltage VSCAN. The matrix elements must therefore be selected and measured sequentially.
The cyclic voltage VSCAN that is applied to a cell typically requires measurement time of seconds to hundreds of seconds per cell. In the case of a DNA chip, the number of cells can increase to well over a thousand resulting in an integration time of hours as each cell is sequentially measured and read out. Also, in order to obtain a repeatable output, the number of cycles is large, which further increases measurement time. Furthermore, some samples may degrade or disintegrate during such long measurement periods, and expensive measures are required to keep them in a stable condition.